Beam damage caused during acquisition of the highest resolution images is the current limitation in the vast majority of experiments performed in a scanning transmission electron microscope (STEM). While the principles behind the processes of knock-on and radiolysis damage are well-known (as are other contributing effects, such as heat and electric fields), understanding how and especially when beam damage is distributed across the entire sample volume during an experiment has not been examined in detail. Here we use standard models for damage and diffusion to elucidate how beam damage spreads across the sample as a function of the microscope conditions to determine an "optimum" sampling approach that maximises the high-resolution information in any image acquisition. We find that the standard STEM approach of scanning an image sequentially accelerates damage because of increased overlap of diffusion processes. These regions of accelerated damage can be significantly decelerated by increasing the distance between the acquired pixels in the scan, forming a "spotscan" mode of acquisition. The optimum distance between these pixels can be broadly defined by the fundamental properties of each material, allowing experiments to be designed for specific beam sensitive materials. As an added bonus, if we use inpainting to reconstruct the sparse distribution of pixels in the image we can significantly increase the speed of the STEM process, allowing dynamic phenomena, and the onset of damage, to be studied directly.Occlusive thrombosis is a central pathological event in heart attack, stroke, thromboembolism, etc. Therefore, pharmacological thrombolysis or anticoagulation is used for treating these diseases. However, systemic administration of such drugs causes hemorrhagic side-effects. Therefore, there is significant clinical interest in strategies for enhanced drug delivery to clots while minimizing systemic effects. One such strategy is by using drug-carrying nanoparticles surface-decorated with clot-binding ligands. Efforts in this area have focused on binding to singular targets in clots, e.g. platelets, fibrin, collagen, vWF or endothelium. Targeting vWF, collagen or endothelium maybe sub-optimal since in vivo these entities will be rapidly covered by platelets and leukocytes, and thus inaccessible for sufficient nanoparticle binding. In contrast, activated platelets and fibrin are majorly accessible for particle-binding, but their relative distribution in clots is highly heterogeneous. We hypothesized that combination-targeting of 'platelets + fibrin' will render higher clot-binding efficacy of nanoparticles, compared to targeting platelets or fibrin singularly. To test this, we utilized liposomes as model nanoparticles, decorated their surface with platelet-binding peptides (PBP) or fibrin-binding peptides (FBP) or combination (PBP + FBP) at controlled compositions, and evaluated their binding to human blood clots in vitro and in a mouse thrombosis model in vivo. In parallel, we developed a computational model of nanoparticle binding to single versus combination entities in clots. Our studies indicate that combination targeting of 'platelets + fibrin' enhances the clot-anchorage efficacy of nanoparticles while utilizing lower ligand densities, compared to targeting platelets or fibrin only. These findings provide important insights for vascular nanomedicine design.A novel copper-catalyzed sulfur dioxide anion incorporation cascade for the synthesis of 1-thiaflavanone sulfones has been disclosed using rongalite as an economic and safe sulfone source. A series of 1-thiaflavanone sulfones were synthesized from easily prepared 2'-iodochalcone derivatives in excellent yields. This transformation proceeds through consecutive formation of two C-S bonds, which is the first example of SO- being used to construct sulfone motifs under copper-catalyzed conditions.Flash vacuum pyrolysis of methyl N-methyl-N-nitrosoanthranilate leads to elimination of nitric oxide and disproportionation of the formed N-radical to 7-(methylamino)phthalide and methyl N-methylanthranilate. This transformation was found to be a convenient, solvent-free method for the preparation of 7-(methylamino)phthalides. An alternative route through pyrolysis of N-benzyl-N-methyl anthranilates was also investigated.Rational molecular structure alterations of TQEN (N,N,N',N'-tetrakis(2-quinolylmethyl)ethylenediamine) produced variable fluorescent sensors for specific metal ions and phosphate species. Utilization of methoxy-substituted quinoline and isoquinoline chromophores, conformational restriction and multidentate coordination structure allow discrimination between Zn2+ and Cd2+. Pyrophosphate (P2O74-, PPi) and phosphate (PO43-) also are selectively detected with dinuclear Zn2+ complexes of tetrakisquinoline-based ligands. Differential stability and structure of the metal complexes, as well as resulting fluorescence enhancement mechanism, such as intramolecular excimer formation via change in coordination geometry, play key roles in the discrimination of target ions.Proteomics has played an important role in elucidating the fundamental processes occuring in living cells. Translating these methods to metallodrug research ('metalloproteomics') has provided a means for molecular target identification of metal-based anticancer agents which should signifcantly advance the research field. https://www.selleckchem.com/products/a-83-01.html In combination with biological assays, these techniques have enabled the mechanisms of action of metallodrugs to be linked to their interactions with molecular targets and aid understanding of their biological properties. Such investigations have profoundly increased our knowledge of the complex and dynamic nature of metallodrug-biomolecule interactions and have provided, at least for some compound types, a more detailed picture on their specific protein-binding patterns. This perspective highlights the progression of metallodrug proteomics research for the identification of non-DNA targets from standard analytical techniques to powerful metallodrug pull-down methods.Recent experiments have reported modified chemical reactivity under vibrational strong coupling (VSC) in microfluidic Fabry-Pérot cavities. In particular, the reaction rate of nucleophilic substitution reactions at silicon centers (SN2@Si) has been altered when a vibrational mode of the reactant was coupled to a confined light mode in the strong coupling regime. In this situation, hybrid light-matter states known as polaritons are formed and seem to be responsible for the modified chemical kinetics. These results are very encouraging for future applications of polaritonic chemistry to catalyze chemical reactions, with the ability to manipulate chemical phenomena without any external excitation of the system. Still, there is no theory capable of explaining the mechanism behind these results. In this work we address two points that are crucial for the interpretation of these experiments. Firstly, by means of electronic structure calculations we report the reaction mechanism in normal conditions of the two recently modified SN2@Si reactions, obtaining in both cases a triple-well PES where the rate-determining step is due to the Si-C and Si-O bond cleavage.